Compositions And Methods For Imaging Immune Cells

Abstract

The present disclosure provides immunes cells comprising a radiolabeled tracer useful in imaging tests such as positron emission topography (PET)/computed tomography (CT) scans. The present disclosure further includes engineered cells comprising a chimeric antigen receptor (CAR) further comprising a nucleic acid molecule comprising a ligand binding domain capable of binding to radiolabeled tracer. This disclosure also includes methods for assessing the efficacy or toxicity of an adoptive cell therapy in a subject, methods for detecting the quantity of engineered T cells in a subject, methods for monitoring an immunotherapy treatment in a subject and methods of imaging engineered T cells in a subject. In some embodiments, the radiolabeled tracer is [ 18 F]fluoropropyl-trimethoprim ([ 18 F]FPTMP).

What is claimed is: 
     
         1 . An engineered cell comprising a chimeric antigen receptor (CAR) and further comprising a nucleic acid molecule comprising a ligand binding domain capable of binding to a radiolabeled tracer. 
     
     
         2 . The engineered cell of  claim 1 , wherein the cell is a T cell. 
     
     
         3 . The engineered cell of  claim 1 , wherein the ligand binding domain is  E. coli  dihydrofolate reductase (eDHFR). 
     
     
         4 . The engineered cell of  claim 1 , wherein the radiolabeled tracer is [ 18 F]fluoropropyl-trimethoprim ([ 18 F]FPTMP). 
     
     
         5 . A method of assessing the efficacy or toxicity of an adoptive cell therapy in a subject, the method comprising:
 a. administering to the subject an engineered T cell comprising a chimeric antigen receptor (CAR) and a nucleic acid molecule comprising a ligand binding domain;   b. administering to the subject a radiolabeled tracer capable of binding to the ligand binding domain;   c. detecting the amount of radiolabeled tracer bound by imaging; and,   d. assessing the efficacy or toxicity of the adoptive cell therapy in the subject.   
     
     
         6 . A method of detecting the quantity of engineered T cells in a subject, the method comprising:
 a. administering to the subject an engineered T cell comprising a chimeric antigen receptor (CAR) and a nucleic acid molecule comprising a ligand binding domain;   b. administering to the subject a radiolabeled tracer capable of binding to the ligand binding domain; and,   c. imaging the amount of radiolabeled tracer bound thereby detecting the quantity of engineered T cells in the subject.   
     
     
         7 . A method of monitoring an immunotherapy treatment in a subject, the method comprising:
 a. administering to the subject an engineered T cell comprising a chimeric antigen receptor (CAR) and a nucleic acid molecule comprising a ligand binding domain;   b. administering to the subject a radiolabeled tracer capable of binding to the ligand binding domain; and,   c. detecting the level of radiolabeled tracer bound by imaging as a measure of the immunotherapy treatment.   
     
     
         8 . The method of  claim 5 , wherein the imaging is performed by positron emission tomography (PET), computerized tomography (CT) or bioluminescence (BL). 
     
     
         9 . A method of imaging engineered T cells in a subject, the method comprising:
 a. administering to the subject an engineered T cell comprising a chimeric antigen receptor (CAR) and a nucleic acid molecule comprising a ligand binding domain;   b. administering to the subject a radiolabeled tracer capable of binding to the ligand binding domain; and,   c. detecting the radiolabeled tracer by imaging using positron emission tomography (PET) or computed tomography (CT).   
     
     
         10 . The method of  claim 5 , wherein the ligand binding domain is  E. coli  dihydrofolate reductase (eDHFR). 
     
     
         11 . The method of  claim 5 , wherein the radiolabeled tracer is [ 18 F]fluoropropyl-trimethoprim ([ 18 F]FPTMP). 
     
     
         12 . The method of  claim 5 , wherein the engineered T cell(s) is/are autologous to the subject. 
     
     
         13 . The method of  claim 5 , wherein the engineered T cell(s) is/are allogenic to the subject. 
     
     
         14 . The method of  claim 5 , wherein the subject is a mammal. 
     
     
         15 . The method of  claim 14 , wherein the mammal is a human.